Oxazolone and pyrrolidinone-substituted biphenyls as P2X

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is:

C 1-6 alkyl; or

halo;

R 2 is:

C 3-6 cycloalkyl;

C 1-6 alkoxy-C 1-6 alkyl;

hydroxy-C 1-6 alkyl; or

heteroaryl-C 1-6 alkyl selected from: pyrazinyl-methyl; pyridazinyl-methyl; pyrimidinyl-methyl; pyrazinyl-ethyl; pyridazinyl-ethyl; pyrimidinyl-ethyl; wherein the pyrazinyl, pyridazinyl and pyrimidinyl portions thereof may be optionally substituted once with methyl;

R 3 is:

ethyl; or

isopropyl;

R 4 is:

hydrogen;

halo;

C 1-6 alkyl;

or R 3 and R 4 together with the atom to which they are attached may form C 3-6 cycloalkyl;

R 5 , R 6 and R 7 each independently is fluoro or hydrogen;

X is: —CR a — wherein R a is hydrogen, C 1-6 alkyl or halo; and

Y is: —O—; —CHR b —;or —NR c —; wherein R b and R c each independently is hydrogen or C 1-6 alkyl.

2. The compound of claim 1 , wherein R 5 , R 6 and R 7 are hydrogen.

3. The compound of claim 2 wherein R 1 is methyl.

4. The compound of claim 2 wherein R 2 is: cyclopropyl; 2-methoxy-1-methyl-ethyl; 2-hydroxy-1-methyl-ethyl; 5-methylpyrazin-2-yl-methyl; 1-pyrazin-2-yl-ethyl; pyrimidin-5-yl-methyl; 6-methyl-pyridazin-3-yl-methyl; pyridazin-3-yl-methyl; 5-methyl-pyrimidin-2-yl-methyl; or 2-methyl-pyrimidin-5-yl-methyl.

5. The compound of claim 2 , wherein R 2 is 2-hydroxy-1-methyl-ethyl; 5-methylpyrazin-2-yl-methyl; or 1-pyrazin-2-yl-ethyl.

6. The compound of claim 2 , wherein R 4 is hydrogen.

7. The compound of claim 2 , wherein R a is hydrogen or halo.

8. The compound of claim 2 , wherein R a is hydrogen.

9. The compound of claim 2 , wherein R a is halo.

10. The compound of claim 2 , wherein Y is —O—.

11. The compound of claim 2 , wherein Y is —CHR b —.

12. The compound of claim 2 , wherein Y is —NR c —.

13. A pharmaceutical composition comprising:

(a) a pharmaceutically acceptable carrier; and

(b) a compound of claim 1 .

14. A method for treating asthma, said method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .

15. A compound selected from:

4′-Methyl-5-(2-oxo-pyrrolidin-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide;

4′-Methyl-5-(2-oxo-imidazolidin-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide;

5 -((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;

5-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;

5-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;

5-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid cyclopropylamide;

5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid cyclopropylamide;

5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;

5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;

5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;

2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;

2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;

2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;

2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid cyclopropylamide;

4′-Methyl-5-(2-oxo-benzooxazol-3-yl)-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;

4′-Methyl-5-(2-oxo-benzooxazol-3-yl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;

4′-Methyl-5-(2-oxo-imidazolidin-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide;

4′-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;

4′-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide; and

4′-Methyl-5-(8-oxo-7,8-dihydro-purin-9-yl)-biphenyl-3-carboxylic acid ((S)-1-pyrazin-2-yl-ethyl)-amide.